3zzz
From Proteopedia
Crystal structure of a Raver1 PRI4 peptide in complex with polypyrimidine tract binding protein RRM2
Structural highlights
Function[PTBP1_HUMAN] Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.[1] [2] [3] [4] [5] [RAVR1_MOUSE] Cooperates with PTBP1 to modulate regulated alternative splicing events. Promotes exon skipping. Cooperates with PTBP1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA.[6] Publication Abstract from PubMedThe polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing. PTB-regulated splicing of alpha-tropomyosin is enhanced by Raver1, a protein with four PTB-Raver1 interacting motifs (PRIs) that bind to the helical face of the second RNA recognition motif (RRM2) in PTB. We present the crystal structures of RRM2 in complex with PRI3 and PRI4 from Raver1, which-along with structure-based mutagenesis-reveal the molecular basis of their differential binding. High-affinity binding by Raver1 PRI3 involves shape-matched apolar contacts complemented by specific hydrogen bonds, a new variant of an established mode of peptide-RRM interaction. Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions. Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB. Crystallographic analysis of polypyrimidine tract-binding protein-raver1 interactions involved in regulation of alternative splicing.,Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S Structure. 2011 Dec 7;19(12):1816-25. PMID:22153504[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
